This project will contribute towards achieving the following broad goals of the CDC: (1) improve the control and prevention of human immunodeficiency virus (HIV) infection, (2) enhance the health of individuals living with HIV infection, and (3) strengthen the capacity nationwide to monitor the HIV epidemic. The specific overall goals of the project are to (1) evaluate the use of dried blood spots (DBS) as a specimen type for surveillance of atypical strains of HIV, (2) monitor the prevalence of atypical strains of HIV among persons newly diagnosed with HIV, and (3) develop a framework for the implementation of routine atypical HIV strain surveillance. HIV genetic diversity has important public health implications for diagnostic testing, clinical monitoring and treatment, vaccine research and evaluation, and epidemiologic monitoring. An efficacious and cost-effective national surveillance system to monitor antiretroviral drug resistance and divergent subtypes of HIV is greatly needed to inform treatment guidelines, to evaluate the accuracy and reliability of current diagnostic and clinical monitoring assays, and to guide resource allocation and program planning for HIV prevention and care services. Briefly, serum/plasma and/or DBS specimens will be collected from at least 140 unique individuals annually who are newly diagnosed with HIV infection in Minnesota and transported to the Minnesota Department of Health (MDH) Public Health Laboratory. HIV genetic material from the specimens will be amplified, sequenced and evaluated for genotypic evidence of antiretroviral drug resistance and subtype determination. Power calculations based on the anticipated specimen numbers and types from the proposed clinical or laboratory participating sites indicate sufficient power to evaluate (1) the accuracy of DBS compared to sera/plasma for determining HIV drug resistance and subtype as well as (2) the resource efficiency of DBS compared to sera/plasma as a specimen type for atypical HIV strain surveillance. Prevalence estimates will also be made for the populations included in the project. Additionally, MDH staff will collaborate with CDC to produce a series of manuscripts that will review the public health importance of national atypical HIV strain surveillance, propose standard genetic loci to sequence for surveillance purposes, provide a template for annual HIV drug resistance and subtype surveillance data reports, and communicate study results regarding the feasibility and efficiency of DBS as a specimen source for atypical HIV strain surveillance.